<b><i>Background:</i></b> Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and is associated with an independent increased risk of lung carcinogenesis. The benefit of chemotherapy for lung cancer in cases of IPF remains unknown. <b><i>Objectives:</i></b> This study was conducted to elucidate the efficacy of chemotherapy for advanced non-small cell lung cancer (NSCLC) in patients with IPF. <b><i>Methods:</i></b> Advanced (i.e. stage IIIB and IV) NSCLC patients with IPF who received systemic chemotherapy were studied. Response rate, toxicity, overall survival and progression-free survival were investigated. <b><i>Results:</i></b> Between January 2000 and December 2009, 21 patients were enrolled in this study and treated with chemotherapy. The overall response rate with the 1st regimen was 42.9%. The median overall survival was 11.4 months, the 1-year survival rate was 28.6% and the median PFS was 5.4 months. <b><i>Conclusions:</i></b> This study showed that advanced NSCLC patients with IPF may benefit from chemotherapy; well-controlled studies are still needed to clarify the efficacy.